Improving the efficacy of anti-EGFR drugs in GBM: Where we are going?

Manxi Ge; Yan Zhu; Minjie Wei; Haozhe Piao; Miao He

doi:10.1016/j.bbcan.2023.188996

Improving the efficacy of anti-EGFR drugs in GBM: Where we are going?

Biochim Biophys Acta Rev Cancer. 2023 Nov;1878(6):188996. doi: 10.1016/j.bbcan.2023.188996. Epub 2023 Oct 5.

Authors

Manxi Ge¹, Yan Zhu¹, Minjie Wei², Haozhe Piao³, Miao He⁴

Affiliations

¹ Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China; Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Shenyang, China.
² Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China; Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Shenyang, China; Liaoning Medical Diagnosis and Treatment Center, Shenyang, China. Electronic address: mjwei@cmu.edu.cn.
³ Department of Neurosurgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China. Electronic address: pzpy@163.com.
⁴ Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China; Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Shenyang, China. Electronic address: hemiao_cmu@126.com.

PMID: 37805108
DOI: 10.1016/j.bbcan.2023.188996

Abstract

The therapies targeting mutations of driver genes in cancer have advanced into clinical trials for a variety of tumors. In glioblastoma (GBM), epidermal growth factor receptor (EGFR) is the most commonly mutated oncogene, and targeting EGFR has been widely investigated as a promising direction. However, the results of EGFR pathway inhibitors have not been satisfactory. Limited blood-brain barrier (BBB) permeability, drug resistance, and pathway compensation mechanisms contribute to the failure of anti-EGFR therapies. This review summarizes recent research advances in EGFR-targeted therapy for GBM and provides insight into the reasons for the unsatisfactory results of EGFR-targeted therapy. By combining the results of preclinical studies with those of clinical trials, we discuss that improved drug penetration across the BBB, the use of multi-target combinations, and the development of peptidomimetic drugs under the premise of precision medicine may be promising strategies to overcome drug resistance in GBM.

Keywords: Combinations; EGFR; Glioblastoma; Stemness; Targeted therapy.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Brain Neoplasms* / drug therapy
Brain Neoplasms* / genetics
Brain Neoplasms* / metabolism
ErbB Receptors
Glioblastoma* / metabolism
Humans
Mutation
Oncogenes

Substances

ErbB Receptors
EGFR protein, human